Cryoanalgesia and Therapeutic Cold
Number: 0297
Table Of Contents
PolicyApplicable CPT / HCPCS / ICD-10 Codes
Background
References
Policy
Scope of Policy
This Clinical Policy Bulletin addresses cryoanalgesia and therapeutic cold.
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Medical Necessity
Aetna considers the following medically necessary:
- The use of cryoanalgesia for the temporary relief of pain due to chronic refractory trigeminal neuralgia (see Appendix for selection criteria);
- Pre-operative, intra-operative, and post-operative cryoanalgesia for post-operative pain management related to the Nuss or Ravitch procedure;
- Passive cold compression therapy units (e.g., Aircast Cryo/Cuff products, the Polar Care Cub, and Polar Care Packs) as medically necessary DME to control swelling, edema, hematoma, hemarthrosis and pain;
- Passive hot and cold therapy. Note: Mechanical circulating units with pumps have not been proven to be more effective than passive hot and cold therapy.
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Experimental and Investigational
The following procedures are considered experimental and investigational because the effectiveness of these approaches has not been established:
- Active cold units with mechanical pumps and portable refrigerators with or without compression therapy (e.g., AutoChill, BioCryo Cold Compression System, Breg Polar Care Cube, Game Ready control units with attached cooling systems, Donjoy IceMan products, Ossur Cold Rush Cold Therapy System, Hilotherm devices, and VPULSE) because they have not been proven to offer clinically significant benefits over passive cold compression therapy units. Note: Aetna considers active cold units with compression therapy experimental and investigational, even if they are only prescribed for the compression component of the device;
- Cryoneurolysis for the treatment of abdominal pain associated with pancreatic cancer, acute pain, cervicogenic headache, chronic head pain secondary to occipital neuralgia, peripheral neuropathic pain, phantom limb pain, and post-herpetic neuralgia;
- Devices that deliver both hot and cold therapy (e.g., Aqua Relief System, Waegener cTreatment, NanoTherm therapy system, ProThermo PT-9 therapy system, Thermacure Contrast Compression Therapy, Kinex ThermoComp device, VascuTherm 4, VascuTherm 5, Recovery+ Thermal Compression System, Thermo Plus-System) for reducing pain and swelling after surgery or injury, or for other indications;
- Intra-operative and post-operative cryoanalgesia for the management of post-thoracotomy pain, and the reduction of post-tonsillectomy pain;
- Passive cold compression therapy units for all other indications (except for the ones listed above);
- Pre-operative cryoneurolysis for pain management following total knee arthroplasty;
- Prophylactic hypothermia for the management of traumatic brain injury;
- Therapeutic hypothermia for the treatment of hemorrhagic stroke;
- Therapeutic induction of intra-brain hypothermia (e.g., pro2cool) for the management of concussion;
- Ultrasound-guided percutaneous intercostal cryoanalgesia for analgesia following mastectomy.
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Related Policies
Background
Cryoanalgesia for Trigeminal Neuralgia
Trigeminal neuralgia (TN), also known as tic douloureux, is a disorder characterized by excruciating episodic pain in the areas innervated by one or more divisions (usually the mandibular and maxillary, rarely the ophthalmic divisions) of the trigeminal nerve. The anti-epileptic drug carbamazepine (Tegretol) is the drug most frequently used for the management of TN. For patients who can not tolerate carbamazepine because of its adverse side effects (poor liver function, confusion, ataxia, drowsiness, and allergic responses), the literature indicates baclofen and other anticonvulsant drugs such as clonazepam (Klonopin) may be useful.
Cryoanalgesia, cryotherapy, or cryoneurotomy has also been used in the treatment of TN. It entails the use of high pressure (approximately 600 pounds per square inch) gas (nitrous oxide or carbon dioxide) administered by a 12- to 14-G needle-shaped cryoprobe. Studies have shown that cryoanalgesia provides temporary pain relief or cure with minimal morbidity (e.g., no permanent sensory loss) in patients with refractory TN.
Intra-Operative and Post-Operative Cryoanalgesia for the Management of Post-Thoracotomy Pain
Thoracotomy, the establishment of an opening into the chest cavity for the management of various cardiopulmonary disorders/diseases, is one of the most painful surgical incisions. Post-thoracotomy pain impairs patients' ability to breathe deeply and cough frequently to prevent atelectasis. Pain relief medication may decrease the coughing reflex as well as depress respiratory functions when the dosage is high enough to achieve analgesia. On the other hand, if the dosage of analgesics is too low to relieve pain, it may render patients with shallow breathing and inadequate coughing reflex. Epidural anesthesia or analgesia may produce some pain relief, but the side effects of severe hypotension, nausea, and urinary retention, as well as the variability of effect limit the usefulness of this approach. Intercostal or paravertebral nerve blocks by means of local anesthetics and severing of the intercostal nerves have also been used to reduce incisional pain following thoracotomy. However, the duration of relief for neural blockade is only a few hours and the procedure is painful, while severing of the intercostal nerves during thoracotomy may result in neuromas, which cause late post-operative pain.
Cryoanalgesia has been used on the intercostal nerves to reduce post-thoracotomy pain. Although the procedure is generally performed prior to closure of the chest at the completion of thoracotomy and may add 10 to 15 mins to the total operating time, it can also be carried out percutaneously in a clinical setting. Cryoanalgesia of the intercostal nerves circumvents the need for repetitive injections of nerve blocks and avoids the toxicity of long acting agents, which may lead to chemically induced intercostal neuritis.
Khanbhai et al (2014) examined if cryoanalgesia improves post-thoracotomy pain and recovery. A total of 12 articles were identified that provided the best evidence to answer the question. The authors, date, journal, study type, population, main outcome measures and results were tabulated. Reported measures were pain scores, additional opiate requirements, incidence of hypoesthesia and change in lung function. Half of the articles reviewed failed to demonstrate superiority of cryoanalgesia over other pain relief methods; however, additional opiate requirements were reduced in patients receiving cryoanalgesia. Change in lung function post-operatively was equivocal. Cryoanalgesia potentiated the incidence of post-operative neuropathic pain. Further analysis of the source of cryoanalgesia, duration, temperature obtained and extent of blockade revealed numerous discrepancies; 3 studies utilized CO2 as the source of cryoanalgesia, and 4 used nitrous oxide but at differing temperatures and duration; 5 studies did not reveal the source of cryoanalgesia. The number of intercostal nerves anesthetized in each study varied; 7 articles anesthetized 3 intercostal nerves, 3 articles used 5 intercostal nerves, 1 article used 4 intercostal nerves and 1 used 1 intercostal nerve at the thoracotomy site. Thoracotomy closure and site of area of chest drain insertion may have a role in post-operative pain; but only 1 article explained method of closure, and 2 articles mentioned placement of chest drain through blocked dermatomes. No causal inferences can be made by the above results as they are not directly comparable due to confounding variables between studies. The authors concluded that currently, the evidence does not support the use of cryoanalgesia alone as an effective method for relieving post-thoracotomy pain.
Humble et al (2015) noted that peri-operative neuropathic pain is under-recognized and often undertreated. Chronic pain may develop after any routine surgery, but it can have a far greater incidence after amputation, thoracotomy or mastectomy. The peak noxious barrage due to the neural trauma associated with these operations may be reduced in the peri-operative period with the potential to reduce the risk of chronic pain. These investigators performed a systematic review of the evidence for peri-operative interventions reducing acute and chronic pain associated with amputation, mastectomy or thoracotomy. A total of 32 randomized controlled trials (RCTs) met the inclusion criteria. Gabapentinoids reduced pain after mastectomy, but a single dose was ineffective for thoracotomy patients who had an epidural. Gabapentinoids were ineffective for vascular amputees with pre-existing chronic pain. Venlafaxine was associated with less chronic pain after mastectomy. Intravenous and topical lidocaine and peri-operative EMLA (eutectic mixture of local anesthetic) cream reduced the incidence of chronic pain after mastectomy, whereas local anesthetic infiltration appeared ineffective. The majority of the trials investigating regional analgesia found it to be beneficial for chronic symptoms. Ketamine and intercostal cryoanalgesia offered no reduction in chronic pain. Total intravenous anesthesia (TIVA) reduced the incidence of post-thoracotomy pain in 1 study, whereas high-dose remifentanil exacerbated chronic pain in another. The authors concluded that- appropriate dose regimes of gabapentinoids, anti-depressants, local anesthetics and regional anesthesia may potentially reduce the severity of both acute and chronic pain for patients;
- ketamine was not effective at reducing chronic pain;
- intercostal cryoanalgesia was not effective and has the potential to increase the risk of chronic pain; and
- TIVA may be beneficial but the effects of opioids are unclear.
Cryoanalgesia for the Post-Operative Pain Management Related to the Nuss Procedure
Sepsas et al (2013) studied patients undergoing thoracotomy to compare the effects of cryoanalgesia, combined with intravenous patient-controlled analgesia (IVPCA), against IVPCA alone during the 4 days following surgery. A total of 50 patients were randomized into 2 groups: an IVPCA group (n = 25) and an IVPCA-cryo group (n = 25). Subjective pain intensity was assessed on a verbal analog scale at rest and during coughing. The intensity and the incidence of post-thoracotomy pain, numbness, epigastric distension and/or back pain, the analgesic requirements, as well as the blood gas values and respiratory function tests were evaluated up to the 2nd post-operative (post-op) month. Hemodynamic data and episodes of nausea and/or vomiting were recorded over the 4 post-op days. In the cryo group there was a statistically significant improvement in postop pain scores (p = 10(-4)), reduction in consumption of morphine (p = 10(-4)) and other analgesics (p = 10(-4)), optimization (less acidosis) of the pH values of blood gases (p < 0.015 over 72 hours post-op and p < 0.03 on the 1st and 2nd post-op months), increase in systolic blood pressure (p < 0.05 over 96 hours post-op), reduction in heart rate (p < 0.05 over 96 hours post-op), increase in values of FEV1 (p < 0.02) and FVC (p < 0.05) at the 1st and 2nd postop months, reduction in the incidence of nausea (0.05 < p < 0.1 over 18 hours post-op), numbness, epigastric distension and back pain (p < 0.05 at days 5, 6, 7, 14, 30 and 60 following surgery). The authors suggested that cryoanalgesia be considered as a simple, safe, inexpensive, long-term form of post-thoracotomy pain relief. Cryoanalgesia effectively restored FEV1 values at the 2nd post-op month.
Keller et al (2016) stated that multi-modal pain management strategies are used for analgesia following pectus excavatum (PE) repair. However, the optimal regimen has not been identified. These researchers described their early experience with intercostal cryoablation for pain management in children undergoing the Nuss procedure and compared early cryoablation outcomes to their prior outcomes using thoracic epidural analgesia. This study was a multi-institutional, retrospective review of 52 patients undergoing Nuss bar placement with either intercostal cryoablation (n = 26) or thoracic epidural analgesia (n = 26) from March 2013 to January 2016. The primary outcome was hospital length of stay (LOS); secondary outcomes included telemetry unit monitoring time, total intravenous narcotic use, duration of intravenous narcotic use, and post-operative complications. Patients who underwent intercostal cryoablation had a significant reduction in the mean hospital LOS, time in a monitored telemetry bed, total use of intravenous narcotics, and the duration of intravenous narcotic administration when compared to thoracic epidural patients. Cryoablation patients had a slightly higher rate of post-operative complications. The authors concluded that intercostal cryoablation is a promising technique for post-operative pain management in children undergoing repair of PE. This therapy resulted in reduced time to hospital discharge, decreased intravenous narcotic utilization, and has eliminated epidurals from the authors’ practice.
Kim et al (2016) noted that although there are reports that showed cryoanalgesia is superior to patient-controlled analgesia (PCA) for post-thoracotomy pain management in the immediate post-operative period, cryoanalgesia for thoracoscopic procedures has not been well described in the literature. In particular, when a patient lies supine, as in the Nuss procedure, the application of a thoracoscopic cryoprobe on the posterolateral intercostal nerves is difficult because of the curvature of the ribs. These researchers described a thoracoscopic transthoracic cryoanalgesia technique applied during the Nuss procedure that overcomes this access difficulty. This method facilitated a cryoprobe application without the need for additional thoracoscopic ports and improved operative field of view.
Graves et al (2017) noted that cryoanalgesia prevents pain by freezing the affected peripheral nerve. These investigators reported the use of intra-operative cryoanalgesia during the Nuss procedure for PE and described their initial experience, modifications of technique, and lessons learned. They retrospectively reviewed the medical records of patients who received cryoanalgesia during the Nuss procedure between June 1, 2015, and April 30, 2016, at their institutions and analyzed modifications in surgical technique during this early adoption period. A total of 8 male and 2 female patients underwent the Nuss procedure with cryoanalgesia. The mean post-operative LOS was 2 days (range of 1 to 3). Average inpatient pain scores were 3.4, 3.2, and 4.6 on post-operative days 1 to 3, respectively (n = 10, 7, and 2). At a 1-week post-operative visit, mean pain score was 1.1 (n = 6). Compared to the preceding 15 Nuss patients at the authors’ institution, who were treated with a thoracic epidural, post-operative LOS was significantly shorter with cryoanalgesia (2.0 ± 0.82 versus 6.3 ± 1.3 days, p < 0.001). These researchers modified their technique for patient habitus and adopted single-lung ventilation for improved visualization. The authors concluded that cryoanalgesia may be the ideal pain management strategy for Nuss patients because it was effective and long-lasting.
Morikawa et al (2018) stated that the Nuss procedure for surgical correction of PE often causes severe post-operative pain. Cryoanalgesia of intercostal nerves is an alternative modality for pain control. These researchers described their modification of the cryoICE™ probe that allowed for nerve ablation through the ipsilateral chest along with early results utilizing this technique. To allow for ipsilateral nerve ablation, a 20-French chest tube was cut and secured to the cryoICE probe, thus providing insulation for the malleable end of the probe. A 3-year retrospective review of patients undergoing Nuss repair at the authors’ institution was performed. Patients who received cryoanalgesia (cryo, n = 6) were compared with a historical control cohort who did not receive cryoanalgesia (non-cryo, n = 13) during Nuss repair. Hospital LOS, post-operative narcotic requirement (PNR), and highest post-operative pain score were collected. Both cohorts were similar regarding age, body mass index (BMI), and pectus index. The cryo group had a significantly less PNR (6.4 versus 17.9 doses, p = 0.05) and was discharged on average more than 1 day earlier than non-cryo patients (3.7 versus 2.2 days, p = 0.01). No complications occurred in either group. The authors concluded that their technique modification simplified previously described approaches to intercostal nerve cryoablation. Patients undergoing this adjunct benefited with less PNR and a faster discharge time.
Graves et al (2019) noted that minimally-invasive repair of PE by the Nuss procedure is associated with significant post-operative pain, prolonged hospital LOS, and high opiate requirement. These researchers hypothesized that intercostal nerve cryoablation during the Nuss procedure reduces hospital LOS compared to thoracic epidural analgesia. This randomized, single-center clinical trial examined 20 consecutive patients undergoing the Nuss procedure for PE between May 2016 and March 2018. Patients were randomized evenly via closed-envelope method to receive either cryoanalgesia or thoracic epidural analgesia. Patients and physicians were blinded to study arm until immediately pre-operatively. A total of 20 consecutive patients were recruited from those scheduled for the Nuss procedure. Exclusion criteria were age of less than 13 years, chest wall anomaly other than PE, previous repair or other thoracic surgery, and chronic use of pain medications. Primary outcome was post-operative LOS; secondary outcomes included total operative time, total/daily opioid requirement, inpatient/outpatient pain score, and complications. Primary outcome data were analyzed by the Mann-Whitney U-test for non-parametric continuous variables. Other continuous variables were analyzed by 2-tailed t-test, while categorical data were compared via Chi-squared test, with alpha = 0.05 for significance. A total of 20 patients were randomized to receive either cryoablation (n = 10) or thoracic epidural (n = 10). Mean operating room (OR) time was 46.5 mins longer in the cryoanalgesia group (p = 0.0001). Median LOS decreased by 2 days in patients undergoing cryoablation, to 3 days from 5 days (Mann-Whitney U, p = 0.0001). Cryoablation patients required significantly less inpatient opioid analgesia with a mean decrease of 416 mg oral morphine equivalent per patient (p = 0.0001), requiring 52 % to 82 % fewer milligrams on post-operative days 1 to 3 (p < 0.01 each day). There was no difference in mean pain score between the groups at any point post-operatively, up to 1 year, and no increased incidence of neuropathic pain in the cryoablation group. No complications were noted in the cryoablation group; among patients with epidurals, 1 patient experienced a symptomatic pneumothorax and another had urinary retention. The authors concluded that intercostal nerve cryoablation during the Nuss procedure decreased hospital LOS and opiate requirement versus thoracic epidural analgesia, while offering equivalent pain control. Level of Evidence = I.
Pilkington et al (2019) noted that intercostal cryoablation(IC) for pain management in children undergoing Nuss Procedure has been previously described. These investigators examined post-operative outcomes following Modified Ravitch procedure for pectus disorders comparing IC to thoracic epidural (TE). This was a single-center, retrospective review of pediatric patients (age of less than 21 years) undergoing Modified Ravitch procedure (January 2015 to March 2019) with either IC (n = 9), or TE (n = 20) analgesia. Primary outcome was LOS; and secondary outcomes were inpatient opioid use (in oral morphine equivalents per kilogram; OME/kg), pain scores on each post-operative day (POD), discharge prescriptions, and complications. Pair-wise comparisons made with Mann-Whitney U test or Fisher Exact test as appropriate; 2-tailed p values of < 0.05 were considered significant. Patient characteristics were similar; LOS was shorter with IC compared to TE (4 days versus 6; p < 0.006). Post-operative opioid use was not significantly different (IC: 1.5 OME/kg versus TE: 1.1; p = 0.10). There was improved pain control on POD 2 in patients who underwent IC (median pain score of 3 versus 4; p < 0.0004). There was no difference in discharge prescription (IC: 3.3 OME/kg; TE: 4.8; p = 0.19) or complication rate (IC: 55.6 %, TE: 50 %; p = 1.0). The authors concluded that IC during the Modified Ravitch reduced LOS compared to TE with improved pain control starting on POD 2, with similar narcotic utilization and complication rates.
Dekonenko et al (2020) noted that pain following bar placement for PE is the dominant factor post-operatively and determines LOS. These researchers recently adopted intercostal cryoablation as their preferred method of pain control following minimally invasive PE repair. They compared the outcomes of cryoablation to results of a recently concluded trial of epidural (EPI) and patient-controlled analgesia (PCA) protocols. These investigators conducted a prospective, observational study of patients undergoing bar placement for PE using intercostal cryoablation. Results were reported and compared with those of a randomized trial comparing EPI with PCA. Comparisons of medians were performed using Kruskal-Wallis H tests with alpha 0.05. A total of 35 patients were treated with cryoablation compared to 32 epidural and 33 PCA patients from the trial. Cryoablation was associated with longer operating time (101 mins versus 58 and 57 mins for epidural and PCA groups, respectively, p < 0.01), resulted in less time to pain control with oral medication (21 hours versus 72 and 67 hours, respectively, p < 0.01), and decreased LOS (1 day versus 4.3 and 4.2 days, respectively, p < 0.01). The authors concluded that intercostal cryoablation during minimally invasive PE repair reduced LOS and peri-operative opioid consumption compared with both EPI and PCA. Level of Evidence = II.
Aiken et al (2021) stated that minimally invasive repair of pectus excavatum (Nuss procedure) is associated with significant pain, and efforts to control pain impact resource utilization. Bilateral thoracic intercostal nerve cryoablation has been proposed as a novel technique to improve post-operative pain control, though the impact on hospital cost is unknown. These researchers carried out a retrospective study of patients undergoing a Nuss procedure from 2016 to 2019. Patients who received cryoablation were compared to those that received traditional pain control (patient-controlled analgesia [PCA] or epidural). Outcome variables included post-operative opioid usage (milligram morphine equivalents, MME), length of stay (LOS), and hospital cost; 35 of 73 patients studied (48 %) received intercostal nerve cryoablation. LOS (1.0 versus 4.0 days, p < 0.01) and total hospital cost ($21,924 versus $23,694, p = 0.04) were decreased in the cryoablation cohort, despite longer operative time (152 versus 74 mins, p < 0.01). Cryoablation was associated with decreased opioid usage (15.0 versus 148.6 MME, p < 0.01) during the 24 hours following surgery and this persisted over the entire post-operative period, including discharge opioid prescription (112.5 versus 300.0 MME, p < 0.01). The authors concluded that bilateral intercostal nerve cryoablation was associated with decreased post-operative opioid usage and decreased resource utilization in pediatric patients undergoing a minimally invasive Nuss procedure for pectus excavatum. Level of Evidence = III.
Rettig et al (2021) stated that the use of intercostal nerve cryoablation (INC) is becoming increasingly common in patients undergoing pectus excavatum (PE) repair. In a retrospective review, these researchers examined the use of INC compared to traditional use of thoracic epidural (TE). A total of 79 patients undergoing PE repair with either INC or TE from May 2009 to December 2019 were evaluated. The operations were carried out by 4 surgeons who worked together at 4 different hospitals and had the same standardized practice. The primary outcome measure was LOS. Secondary variables included surgical time, total operating room time, operating room (OR) time cost, total hospital cost, inpatient opioid use, long-term opioid use after discharge, and post-operative complications. LOS decreased to 2.5 days in the INC group compared to 5 days in the TE group (p < 0.0001). Surgical time was increased in the INC group, but there was no difference in total OR time. The INC group experienced significantly lower hospital costs. Total hospital opioid administration was significantly lower in INC group, and there was a significant decrease in long-term opioid use in the INC group. The authors concluded that INC is a newer modality that decreased LOS, controlled pain, and resulted in overall cost savings. These investigators recommended that INC be included in the current practice for post-operative pain control in PE patients undergoing Nuss procedure.
Velayos and colleagues (2021) noted that in recent years, pain protocols for PE have incorporated cryoanalgesia via thoracoscopic approach. Since 2019, US-guided percutaneous cryoanalgesia (PCr) has been used at the authors’ institution, either on the same day as the Nuss procedure or 48 hours before surgery. They performed a preliminary retrospective review of patients with PE in whom PCr before surgery between 2019 and 2021. Two groups were evaluated: PCr on the same day (PCrSD) and PCr 48 hours before surgery (PCr48). Despite PCr, patients were treated with PCA with opioids for at least 24 hours, switching to conventional intravenous analgesia and oral analgesia in the following days. Demographic, clinical-radiological variables, PCA opioid use, pain grade according to the VAS, and hospital LOS were compared between the groups. A total of 20 patients were included (12 with PCrSD and 8 with PCr48), without significant differences in demographics or clinical-radiological variables. The overall median time of PCr was 65 mins (55 to 127), with no differences between the groups. PCr48 group presented with significantly lower median number of hours of continuous PCA (24 versus 32 hours; p = 0.031), lower median number of rescue boluses (11 versus 18; p = 0.042), lower median VAS in the early post-operative hours (2 versus 5.5; p = 0.043), and lower median LOS (3.5 versus 5 days). The authors concluded that PCr performed 48 hours before surgery was more effective in terms of PCA requirements, VAS, and LOS when compared with cryoanalgesia on the same day.
In a retrospective, single-center, cohort study, Arshad and associates (2022) examined the impact that cryoanalgesia had on opioid utilization and outcomes of pediatric patients undergoing MIRPE; patients were less than 18 years of age who underwent MIRPE between 2011and 2019. Patients receiving cryoanalgesia were compared to those who did not. The primary outcome was total post-operative opioid use, total inpatient opioid use, measured as milligrams of oral morphine equivalents per kilogram (OME/kg) of body weight. Univariate and multivariable analyses were performed. Of 35 patients, 20 received cryoanalgesia (57 %); baseline characteristics were similar. Patients who received cryoanalgesia had a lower opioid requirement: median of 2.3 mg OME/kg (IQR 1.2 to 3.1), versus 4.9 mg OME/kg (IQR 2.9 to 5.8), p < 0.001. Accounting for receipt of cryoanalgesia, epidural, and/or PCA, cryoanalgesia was associated with a 3.3 mg OME/kg reduction in opioid use (p < 0.001). Median hospital LOS was shorter in cryoanalgesia patients: 3.1 days (IQR 2.3 to 3.4), versus 5.1 days (IQR 4.3 to 5.4), p < 0.001. Complications within 90 days were similar between groups. The authors concluded that cryoanalgesia was an effective adjunctive pain control modality for patients undergoing MIRPE. Use of cryoanalgesia was associated with lower post-operative opioid requirements and shorter hospital LOS, without increased short-term complications, and should be considered for enhanced recovery after MIRPE.
Cold Therapy Units and Hot/Ice Machine
Cold therapy devices combine cold temperatures and compression to decrease discomfort and swelling following injury or surgery to an extremity. The theory behind cold therapy is that by decreasing the temperature of the tissue, which produces vasoconstriction, pain is lessened, muscle spasm is decreased and inflammation is reduced.
Active cold therapy devices and combined heat and cold therapy devices utilize pneumatic or mechanical pumps that may be battery or electrically operated. The intended function of the pump is to provide cyclical compression and cooling or heating to the affected area. The devices generally consist of two basic parts: a wrap or wrap system and a control unit or pump, which is filled with ice and/or water. The control unit or pump circulates the cooled or heated water through the wrap system to the affected area.
Active Cooling or Heating Devices
Examples of active cooling or heating devices include, but may not be limited to:
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Auto Chill Device
- Cold therapy device in which a pump is used in conjunction with the Cryo/Cuff System. The pump automatically exchanges water from the pump to the cooler and eliminates the need for manual water recycling.
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cTreatment
- Computer controlled heat and cold.
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Hilotherm
- Heat and cold water pump with pads.
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Game Ready Accelerated Recovery System
- System that combines cold and intermittent pneumatic compression therapies. It includes a computer that controls treatment time, level of compression and temperature. The unit continuously cycles liquid through circumferential wraps for consistent, long lasting cold treatment, even over large surface areas.
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Hot/Ice Thermal Blanket
- Provides heat/cold therapy by the application of rubber pads (blankets) that are connected by a hose to a main cooling unit. The pads receive fluid that has circulated from the main unit and can be either hot or cold.
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IceMan Cryotherapy Unit
- Utilizes a semi-closed loop system with a mechanical pump that allows warm water to circulate, at a constant flow rate, with cooler water providing consistent cold distribution throughout the pad.
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Kinex ThermoComp Device
- Another example of a device that combines cold therapy with intermittent pneumatic compression.
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NanoTherm
- System that combines cold or heat with intermittent pneumatic compression therapies.
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Ossur Cold Rush Cold Therapy System
- Combines cold pump with compression.
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Thermocure Contrast Compression Therapy
- Combines heat or cold pump with compression.
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VitalWrap System
- Consists of three components: a control unit, a tubing set and a thermal fabric wrap. The control unit, which includes a fluid reservoir, manages the temperature of water used by the system to supply heat or cold to the fabric wrap attached to the body. Compression is delivered through the wrap itself.
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VPULSE
- Intermittent pneumatic compression with cold water pump.
Passive cold therapy devices operate by gravity or a hand pump without the use of a battery or electricity. Generally, they consist of a cuff or wrap and a cooler. Ice water is placed in the reservoir or cooler. The cooler is placed above the affected body area or joint and then utilizes gravity to fill the cuff and compress the joint.
Passive Cold Therapy Devices
Examples of passive cold therapy devices include, but may not be limited to:
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AirCast Cryo/Cuff System
- Therapy system consisting of a cuff, a cooler and a hose. The hose exchanges cooled ice water between the cooler and the cuff which covers the injured area. Elevating the cooler fills and pressurizes the cuff. Compression is controlled by gravity and is proportional to the elevation of the cooler.
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Polar Care (PC) Cub Unit
- Cold therapy system which includes a PC Cub cooler, manual pump and wrap on pads. The pads are held in place with elastic straps or an ace wrap. The built-in hand pump circulates the cold water through the polar pad, while at the same time increases the compression around the joint.
Cold therapy units are devices in which fluid flows through a blanket or cuff, providing immediate cooling to an affected area. The AirCast Cryo/Cuff uses a insulated jug filled with cold water attached to a cuff. Elevating the jug fills and pressurizes the cuff. Compression is controlled by gravity, and is proportional to the elevation of the cooler. When body heat warms the water, it is re-chilled simply by lowering the cooler. Another passive cold compression therapy unit is the Polar Care Cub unit.
More complicated cold therapy units may employ mechanical pumps and refrigerators that are powered by battery or electricity (e.g., IceMan). The Game Ready system is an example of an active cooling device that combines cold and intermittent pneumatic compression therapies. The system consists of a wrap, a connector hose, and a control unit. The wrap contains two internal chambers, one for air and the other for cooling water. The microprocessor control unit features various adjustable compression cycles and temperature controls. However, there is no evidence that these more complicated cold therapy units provide any additional benefit over the CryoCuff or conventional ice bags or packs. Aetna's current policy on mechanical cold therapy pumps is consistent with Medicare DME MAC policy.
Leutz and Harris (1995) described a retrospective study that assessed 52 consecutive patients who underwent total knee arthroplasty (TKA). A total of 33 patients underwent TKA and received cold therapy pads placed over a thin dressing in the operating room; 19 patients underwent TKA using an identical operative and post-operative procedure, but did not receive continuous cold therapy. Continuous cold therapy consisted of 2 sterile plastic pads connnected by rubber hoses containing cool water from an electric main unit that maintained a constant temperature of 42 degrees F for the immediate post-operative period. Cold therapy pads were used an average of 3 days and removed with the first dressing change. Patients who had continuous cold therapy averaged a 200 ml decrease in post-operative blood loss. There was no significant difference in the amount of narcotic use, transfusion requirements, or hospital stay between the two groups. Post-operative swelling and range of motion were not consistently recorded. Twenty-eight other variables were also examined, but no significant differences were found between groups. Based on these results, the authors stated that they can not recommend continuous cold therapy or justify the extra expense for all patients who undergo TKA.
A Hot/Ice Machine consists of 2 rubber pads connected by a rubber hose to a unit that circulates hot or cold fluid through the pads. Studies in the published literature have been poorly designed and have failed to show that the Hot/Ice Machine offers any benefit over standard cryotherapy with ice packs, and there are no studies evaluating the use of this device as a heat source.
The VitalWrap (VitalWear Inc. South San Francisco, CA) is an active heating/cooling device that allows the user to circulate either hot or cold fluid through the system. The VitalWrap system consists of a bladder filled body wrap/pad, tubing, and a reservoir/pump device. Cooled or heated water may be added to the pump reservoir and then circulated through the tubing to the body wrap/pad and then back to the reservoir. The benefits of this type of device above other cooling or heating methods have not been established at this time.
Vascutherm (ThermoTek, Carrollton, TX) is an active cold compression therapy unit with a pneumatic pump. It provides heating, cooling and compression therapies. The device also includes a deep vein thrombosis (DVT) mode -- this is a compression (or air) only mode, that is intended to prevent DVT. However, it provides no additional clinical utility or impact on health outcomes than the use of ice or compression wraps.
The TEC Thermoelectric Cooling System (Maldonado Medical, Phoenix, AZ) is marketed to reduce post-operative pain and edema. It is an iceless cold therapy compression/DVT prophylaxis machine that can also provide heat. It is limited to a cold temperature of 49 degrees F to minimize the potential for frostbite. However, it provides no additional clinical utility or impact on health outcomes than the use of ice or compression wraps.
According to the manufacturer, the Kinex ThermoComp™ Device provides 3 separate pre-programmed therapies that are activated by a push of a button:- cold-compression,
- contrast-compression, and
- intermittent pneumatic compression for DVT prophylaxis.
Continuous cold is delivered by a solid-state system without ice. Cold temperature is microprocessor-controlled within 1° making this one of the safest devices for unsupervised use in a patient's home. Contrast therapy cycles every 30 mins with cold at 49° for 20 mins followed by heat at 105° for 10 mins. Intermittent compression is delivered distal-to-proximal through a segmented pad. Deep vein thrombosis prophylaxis is delivered from a rapid inflation pump at 50 mm Hg through a calf pad or 100 mm Hg through a foot pad. All 3 therapies are delivered separately, however cold-compression and DVT compression can run at the same time with the device cycling DVT compression separate from limb compression. The Kinex ThermoComp™ Device is intended to treat post-operative injuries in the home, to reduce edema and pain, to improve blood flow to the surgical site, and to provide DVT prophylaxis therapy for high-risk patients. However, there is a lack of evidence regarding the safety and effectiveness of this device.
According to the manufacturer, the VascuTherm2 solid state device provides heat, cold (without ice), compression, and/or DVT prophylaxis therapy. The system is pre-programmed per written physician's instructions for fully automatic, safe, trouble-free use in the patient's home. It is indicated for pain, edema, and DVT prophylaxis for the post-operative orthopedic patient. The precisely controlled temperature range of 43 degrees F to 105 degrees F insures against frost-bite or burns. Therapy times are also pre-programmed to insure maximum patient compliance. It is extremely easy for patients to set up and use. However, there is a lack of evidence regarding the safety and effectiveness of this device.
Intra-Operative and Post-Operative Cryoanalgesia for Reduction of Post-Tonsillectomy Pain
In a systematic review, Raggio and colleagues (2018) examined the effectiveness of intra-operative cryoanalgesia in the management of post-operative pain among patients undergoing palatine tonsillectomy. These investigators performed a systematic review of PubMed, Medline, Embase, Google Scholar, and Cochrane trial registries through January 2017 using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) standards. They included English-language RCTs evaluating patients of all age groups with benign pathology who underwent tonsillectomy with cryoanalgesia versus without. A total of 3limited quality RCTs involving 153 participants (age range of 1 to 60 years) were included. Cryoanalgesia was performed with a cryotherapy probe (-56°C) in 1 trial and ice-water cooling (4°C to 10°C) in 2. In the 3 trials reviewed, patients who received cryoanalgesia reported 21.38 %, 28.33 %, and 31.53 % less average relative post-operative pain than controls on the visual analog scale (VAS). Review of secondary outcomes suggested no significant difference in time to resume normal diet (2 studies) or post-operative bleeding (2 studies) between the 2 groups. Cryoanalgesia allowed patients to return-to-work 4 days earlier than controls in 1 study; 2 studies reported a trend toward less post-operative analgesia use among the treatment group; however, no statistical conclusions could be drawn. The authors concluded that available evidence suggested that patients undergoing tonsillectomy with cryoanalgesia experienced less average post-operative pain without additional complications. These preliminary findings need to be validated by well-designed studies.
Furthermore, UpToDate reviews on “Tonsillectomy (with or without adenoidectomy) in children: Postoperative care and complications” (Messner, 2019), “Tonsillectomy in adults” (Gibber, 2019), and “Anesthesia for tonsillectomy with or without adenoidectomy in children” (Sadhasivam, 2019) do not mention intra-operative and post-operative cryoanalgesia as a management option.
Prophylactic Hypothermia for the Management of Traumatic Brain Injury
Cooper and colleagues (2018) stated that after severe traumatic brain injury (TBI), induction of prophylactic hypothermia has been suggested to be neuro-protective and improve long-term neurologic outcomes. These researchers examined the effectiveness of early prophylactic hypothermia compared with normothermic management of patients after severe TBI. The Prophylactic Hypothermia Trial to Lessen Traumatic Brain Injury-Randomized Clinical Trial (POLAR-RCT) was a multi-center, randomized trial in 6 countries that recruited 511 patients both out-of-hospital and in emergency departments (EDs) after severe TBI. The first patient was enrolled on December 5, 2010, and the last on November 10, 2017. The final date of follow-up was May 15, 2018. There were 266 patients randomized to the prophylactic hypothermia group and 245 to normothermic management. Prophylactic hypothermia targeted the early induction of hypothermia (33° C to 35° C) for at least 72 hours and up to 7 days if intra-cranial pressures were elevated, followed by gradual re-warming. Normothermia targeted 37° C, using surface-cooling wraps when required. Temperature was managed in both groups for 7 days. All other care was at the discretion of the treating physician. The primary outcome was favorable neurologic outcomes or independent living (Glasgow Outcome Scale-Extended score, 5 to 8 [scale range of 1 to 8]) obtained by blinded assessors 6 months after injury. Among 511 patients who were randomized, 500 provided ongoing consent (mean age of 34.5 years [SD, 13.4]; 402 men [80.2 %]) and 466 completed the primary outcome evaluation. Hypothermia was initiated rapidly after injury (median of 1.8 hours [inter-quartile range [IQR], 1.0 to 2.7 hours]) and re-warming occurred slowly (median of 22.5 hours [IQR, 16 to 27 hours]). Favorable outcomes (Glasgow Outcome Scale-Extended score, 5 to 8) at 6 months occurred in 117 patients (48.8 %) in the hypothermia group and 111 (49.1 %) in the normothermia group (risk difference, 0.4 % [95 % confidence interval [CI]: -9.4 % to 8.7 %]; relative risk (RR) with hypothermia, 0.99 [95 % CI: 0.82 to 1.19]; p = 0.94). In the hypothermia and normothermia groups, the rates of pneumonia were 55.0 % versus 51.3 %, respectively, and rates of increased intra-cranial bleeding were 18.1 % versus 15.4 %, respectively. The authors concluded that among patients with severe TBI, early prophylactic hypothermia compared with normothermia did not improve neurologic outcomes at 6 months. These findings did not support the use of early prophylactic hypothermia for patients with severe TBI.
Guidelines on management of severe traumatic brain injury from the Brain Injury Foundation (Carney, et al., 2017) concluded that early (within 2.5 hours), short-term (48 hours post-injury) prophylactic hypothermia is not recommended to improve outcomes in patients with diffuse injury.
Therapeutic Induction of Intra-Brain Hypothermia for Concussion Management
The pro2cool system (TecTraum Inc.), which received FDA Breakthrough Device designation in June 2021, is a novel, noninvasive, portable hypothermic therapy device aimed at reducing the severity of concussion symptoms. Following a suspected concussion, or within eight days of a head injury, the pro2cool system is applied to the patient's head and neck, providing cooling to the carotid arteries to decrease the temperature of the blood before it enters the brain, potentially reducing the effects of brain trauma by reducing the inflammatory response to the head injury. The pro2cool technology does not require ice. This portable system uses “high-tech” software to cool the patient to the appropriate temperature and holds them there for the duration of the two 30-minute treatments (TecTraum, 2022b). The pro2cool system includes therapeutic induction of intra-brain hypothermia, including placement of a mechanical temperature-controlled cooling device to the neck over carotids and head, including monitoring (e.g., vital signs and sport concussion assessment tool 5 [SCAT5]), 30 minutes of treatment.
Gard et al (2021) aimed to investigate whether selective head–neck cooling could shorten recovery after sports-related concussions (SRCs). The authors conducted a nonrandomized study of 15 Swedish professional ice hockey teams and evaluated 29 concussed players who received immediate head and neck cooling for 30 min or more (initiated at 12.3 ± 9.2 min post-SRC by a portable cooling system), and 52 SRC controls who received standard management. The authors found that players receiving head–neck cooling had shorter time to return-to-play than controls (7 vs 12.5 days, p < 0.0001), and 7% in the intervention group versus 25% in the control group were out of play for 3 weeks or more (p = 0.07). The authors concluded that immediate selective head–neck cooling is a promising option in the acute management of SRC that should be addressed in larger cohorts.
Congeni et al (2022) conducted a randomized, nonblinded, pilot study at a sports medicine clinic to determine the safety and efficacy of head and neck cooling when applied up to 8 days after concussion among adolescent athletes (aged 12 to 17 years diagnosed with a concussion within 1 week of injury). The control group (n = 27) received standard treatment (short term brain rest), whereas the treatment group (n = 28) received standard treatment and head and neck cooling. Head and neck cooling treatment was applied to patients at the postinjury assessment visit and at 72 hours post-injury. The SCAT5 (Sport Concussion Assessment Tool) total symptom severity score was collected at postinjury assessment visit, pre- and post-treatment at 72 hours, and at 10 days, and 4 weeks post-treatment. The authors found that athletes who received head and neck cooling had a faster symptom recovery (p = 0.003) and experienced significant reduction in symptom severity scores after treatment (p< 0.001). Sport type and gender did not influence the treatment outcome (p= 0.447 and 0.940, respectively). The authors concluded that this pilot study demonstrates feasibility of head and neck cooling for the management of acute concussion in adolescent athletes.
Al-Husseini and colleagues (2022) state that an exercise-induced elevation of core body temperature is associated with increased brain temperature that may accelerate secondary injury processes following a sports-related concussion (SRC), and exacerbate the brain injury. The authors extended the Gard et al (2021) clinical trial to include players of 19 male elite Swedish ice hockey teams over five seasons (2016-2021). In the intervention teams, acute head-neck cooling was implemented using a head cap for 45 min or more in addition to the standard SRC management used in controls. The primary endpoint was time from SRC until return-to-play (RTP). Sixty-one SRCs were included in the intervention group and 71 SRCs in the control group. The number of previous SRCs was 2 (median and interquartile range [IQR]: 1.0-2.0) and 1 (IQR 1.0-2.0) in the intervention and control groups, respectively; p = 0.293. Median time to initiate head-neck cooling was 10 min (IQR 7-15; range 5-30 min) and median duration of cooling was 45 min (IQR 45-50; range 45-70 min). The median time to RTP was 9 days in the intervention group (IQR 7.0-13.5 days) and 13 days in the control group (IQR 9-30; p< 0.001). The proportion of players out from play for more than the expected recovery time of 14 days was 24.7% in the intervention group, and 43.7% in controls (p < 0.05). The authors note that study limitations include that: 1) allocation to cooling or control management was at the discretion of the medical staff of each team, decided prior to each season, and not by strict randomization; 2) no sham cap was used and evaluations could not be performed by blinded assessors; and 3) it could not be established with certainty that injury severity was similar between groups. The authors concluded that while the results should thus be interpreted with caution, early head-neck cooling, with the aim of attenuating cerebral hyperthermia, may reduce post-SRC symptoms and lead to earlier return-to-play in elite ice hockey players.
The pro2cool device is not currently cleared for use by the FDA. TecTraum Inc. plans to submit data outcomes from a clinical trial that was completed in April 2022 for publication in April 2023, and to the FDA for consideration of market authorization in May 2023. The goal for commercial launch is set for late 2023 (TecTraum, 2022a).
Therapeutic Hypothermia for the Treatment of Hemorrhagic Stroke
Choi and associates (2017) noted that therapeutic hypothermia (TH) improves the neurological outcome in patients after cardiac arrest and neonatal hypoxic brain injury. In a pilot study, these researchers studied the safety and feasibility of mild TH in patients with poor-grade subarachnoid hemorrhage (SAH) after successful treatment. Patients were allocated randomly to either the TH group (34.5° C) or control group after successful clipping or coil embolization. A total of 11 patients received TH for 48 hours followed by 48 hours of slow re-warming. Vasospasm, delayed cerebral ischemia (DCI), functional outcome, mortality, and safety profiles were compared between groups. These investigators enrolled 22 patients with poor-grade SAH (Hunt & Hess Scale 4, 5 and modified Fisher Scale 3, 4). In the TH group, 10 of 11 (90.9 %) patients had a core body temperature of less than 36° C for greater than 95 % of the 48-hour treatment period. Fewer patients in the TH than control group (n = 11, each) had symptomatic vasospasms (18.1 % versus 36.4 %, respectively) and DCI (36.3 % versus 45.6 %, respectively), but these differences were not statistically significant. At 3 months, 54.5 % of the TH group had a good-to-moderate functional outcome (0 to 3 on the modified Rankin Scale [mRS]) compared with 9.0 % in the control group (p = 0.089). Mortality at 1 month was 36.3 % in the control group compared with 0.0 % in the TH group (p = 0.090). the authors concluded that mild TH was feasible and could be safely used in patients with poor-grade SAH. Furthermore, it may reduce the risk of vasospasm and DCI, improving the functional outcomes and reducing mortality. Moreover, these researchers stated that larger randomized controlled studies should be conducted to determine the safety and clinical impact of TH in poor-grade SAH patients following successful intervention.
The authors stated that this study had several drawbacks. First, this was a pilot study and should be interpreted with caution. Second, the observed clinical benefits of hypothermia were limited because of the small sample size (n = 11). A larger sample size may be needed to identify a meaningful difference between TH and control groups. Third, despite well-designed neuro-critical care treatment guidelines, a hidden bias may exist between TH and control groups in critical care because the treating physicians were not double-blinded. Fourth, the induction time of TH was confined after successful intervention. Fifth, the different use of cooling devices was not reflected in TH group.
Yao and colleagues (2018) stated that TH has shown good results in experimental models of hemorrhagic stroke. The clinical application of TH, however, remains controversial, since reports regarding its therapeutic effect were inconsistent. These researchers conducted a systematic review based on PRISMA comparing TH with a control group in terms of mortality, poor outcome, DCI, and specific complications. The subgroup analyses were stratified by study type, country, mean age, hemorrhage type, cooling method, treatment duration, rewarming velocity, and follow-up time. A total of 9 studies were included, most of which were of moderate quality. The overall effect demonstrated insignificant differences in mortality (risk ratio [RR] 0.78; 95 % CI: 0.58 to 1.06; p = 0.11) and poor outcome rate (RR 0.89; 95 % CI: 0.70 to 1.12; p = 0.32) between TH and the control group. However, sensitivity analyses, after omitting 1 study, achieved a statistically significant difference in poor outcome favoring TH. Moreover, in the subgroup analyses, the results derived from randomized studies revealed that TH significantly reduced poor outcomes (RR 0.40; 95 % CI: 0.22 to 0.74; p = 0.003). In addition, TH significantly reduced DCI compared with control (RR 0.61; 95 % CI: 0.40 to 0.93; p = 0.02). The incidence of specific complications (re-bleeding, pneumonia, sepsis, arrhythmia, and hydrocephalus) between the 2 groups were comparable and did not reach significant difference. The authors concluded that the overall effect showed TH did not significantly reduce mortality and poor outcomes but led to a decreased incidence of DCI. Compared with control, TH resulted in comparable incidences of specific complications.
Cryoanalgesia for Post-Operative Analgesia in Repair of Pectus Excavatum
Parrado and colleagues (2019) noted that cryoanalgesia has been applied to minimally invasive repair of pectus excavatum (MIRPE). After implementation of cryoanalgesia at the authors’ institution, these researchers had several cases of delayed post-operative pneumothorax. These investigators examined the complications and efficacy of cryoanalgesia in MIRPE. They carried out a single-center retrospective review of pediatric patients undergoing MIRPE from June 2017 to July 2018. Multi-modal (MM) analgesia was used in all patients. In addition, most patients received either cryoanalgesia or elastomeric pain pumps (EPPs) as adjuncts to post-operative analgesia. Primary outcome was clinically significant late pneumothorax; and secondary outcomes included length of stay, pain scores, opiate use, and bar displacement requiring re-operation. A total of 101 patients undergoing MIRPE were included: 45 had cryoanalgesia + MM, 45 EPP + MM, and 11 MM alone. Post-operative tube thoracostomy was placed in 5 patients with cryoanalgesia (4 pneumothorax; 1 effusion), 1 patient with EPP (1 pneumothorax), and none in MM alone (p = 0.25). Pain scores at discharge were similar in all groups. Cryoanalgesia patients received less overall in-patient opioids than other groups (p < 0.05). No patient required re-operation for bar displacement. The authors concluded that cryoanalgesia was an effective therapy for pain control in MIRPE. Because thermal injury could occur on the lung and chest wall with cryoanalgesia, these researchers implemented techniques to limit and prevent this injury. They stated that cryoanalgesia offered a safe alternative for post-operative analgesia with significant reduction in inpatient opioid requirement. Moreover, they stated that larger prospective studies are needed to examine the long-term impact and complications of cryoanalgesia.
Cryoneurolysis for the Treatment of Post-Herpetic Neuralgia
An evidence-based report on treatment of ost-herpetic neuralgia (PHN) was developed by the Quality Standards Subcommittee of the American Academy of Neurology (Dubinsky et al, 2004) and it stated that the effectiveness of carbamazepine, nicardipine, biperiden, chlorprothixene, ketamine, Helium:Neon (He:Ne) laser irradiation, intralesional triamcinolone, cryocautery, topical piroxicam, extract of Ganoderma lucidum, dorsal root entry zone lesions and stellate ganglion block are unproven in the treatment of PHN.
Weber and colleagues (2019) noted that PHN is a common and potentially debilitating neuropathic pain condition. Current pharmacologic therapy can be inadequate and intolerable for patients. These researchers presented a case of a man with refractory PHN in the intercostobrachial nerve (ICBN) distribution that was successfully treated with cryoneurolysis / cryoanalgesia therapy. Given the severity of PHN and disabling pain to patients with limited options, these investigators believed that cryoablation offers an alternative that is minimally invasive, with less risk compared to other forms of neurolysis. This case-report showed an ICBN neuralgia related to PHN, which to the authors’ knowledge has not been reported in the literature and treated with cryoablation. While the authors acknowledged that additional studies are needed and the conflicting data on efficacy of cryoablation with intercostal blocks and with post-thoracotomy pain, there have been positive results for cryoanalgesia for PHN in the dermatologic literature with cutaneous use. Furthermore, the minimal risk to ICBN cryoablation given the superficial nature, as compared to intercostal blocks, whose risks include pneumothorax and vascular uptake / bleeding, allowed for the ICBN cryoanalgesia to be a viable option that should be further examined in patients who presented with features of ICBN neuralgia related to PHN.
Furthermore, an UpToDate review on “Postherpetic neuralgia” (Ortega, 2020) states that “Cryotherapy involves freezing peripheral nerves. A small, unblinded study of cryotherapy for facial pain was unable to show a significant benefit in patients with PHN [89]. The authors did not provide inclusion criteria, concomitant therapies, or information on how the response was assessed. By contrast, a second trial reported "considerable" relief in 11 of 14 patients with cryotherapy to the intercostal nerves for PHN [90]. In most cases, however, the duration of relief was less than two weeks as assessed by questionnaire”.
Ultrasound-Guided Percutaneous Intercostal Cryoanalgesia for Analgesia Following Mastectomy
Gabriel and colleagues (2020) stated that acute post-mastectomy pain is frequently challenging to adequately treat with local anesthetic-based regional anesthesia techniques due to its relatively long duration measured in multiple weeks. These investigators reported 3 cases in which pre-operative ultrasound (US)-guided percutaneous intercostal nerve cryoneurolysis was performed to treat pain following mastectomy. Across all post-operative days and all 3 patients, the mean pain score on the numeric rating scale (NRS) was 0 for each day. Similarly, no patient required any supplemental opioid analgesics during the entire post-operative period; and, no patient reported insomnia or awakenings due to pain at any time-point. This was a significant improvement over historic controls. The authors concluded that US-guided percutaneous cryoanalgesia is a potential novel analgesic modality for acute pain management that had a duration that better-matched mastectomy than other currently-described techniques. These researchers stated that appropriately powered RCTs are needed to determine and quantify both potential benefits and risks.
Cryoneurolysis for the Treatment of Abdominal Pain associated with Pancreatic Cancer
Filippiadis and colleagues (2021) reported their preliminary results on the feasibility, safety and efficacy of percutaneous splanchnic nerves cryoneurolysis for the treatment of abdominal pain refractory to conservative medication in patients with pancreatic cancer. Institutional database research (retrospective review of prospectively collected data from April 2019 till August 2020) identified 5 patients with pancreatic cancer and pain refractory to conservative medication who underwent percutaneous cryoneurolysis of splanchnic nerves. In all subject, percutaneous cryoneurolysis was carried out with posterolateral paravertebral approach using a 17-G cryoprobe under computed tomography (CT) guidance and local anesthesia. Self-reported pain scores were assessed before and at the last follow-up using a pain inventory with VAS units. Mean patient age was 63.81 years (male-female: 3-2). Mean pain score prior to cryoanalgesia of splanchnic nerves was 9.4 VAS units. This score was reduced to a mean value of 2.6, 2.6 and 3 VAS units at 1, 3 and 6 months of follow-up, respectively. All patients reported significantly reduced analgesic usage. No complication was reported according to the CIRSE classification system. The mean procedure time was 44.4 mins (range of 39 to 50 mins), including local anesthesia, cryoprobe(s) placement, ablation and post-procedural CT evaluation. The authors concluded that percutaneous cryoanalgesia of the splanchnic nerves is a minimally invasive, safe and effective procedure for pancreatic cancer pain relief. Moreover, these researchers stated that a larger, randomized trial is needed to validate these findings.
Cryoneurolysis for the Treatment of Cervicogenic Headache
Kvarstein and colleagues (2019) noted that cervicogenic headache (CEH) is a debilitating condition and analgesics have limited effect; thus, percutaneous cryoneurolysis is still in use despite a lack of clinical evidence. In a RCT, these researchers compared the effectiveness of cryoneurolysis with a corticosteroid combined with a local anesthetic. They carried out a double-blinded, comparative study with an 18-week follow-up. After positive diagnostic test blocks, a total of 52 eligible patients were randomly allocated in a ratio of 3:2 -- 31 subjects to occipital cryoneurolysis and 21 subjects to injections of 1-ml methylprednisolone 40 mg/ml (Depo-Medrol) combined with 1-ml bupivacaine 5 mg/ml. These researchers observed a significant pain reduction of more than 50 % in both therapeutic groups, slightly improved neck function and reduced number of opioid consumers. However, after 6 to 7weeks, pain intensity increased gradually, but did not reach baseline within 18 weeks. Although cryoneurolysis provided a more prolonged effect, the group differences did not reach statistical significance. Health related quality of life (HR-QOL) and psychological distress improved minimally. A large number reported minor and transient side effects, but these investigators found no significant group differences. After 18 weeks, 29 % rated the headache as much improved, and 12 (24 %) somewhat improved, but a large proportion (78 %) reported need for further intervention/treatment. The authors concluded that cryoneurolysis provided substantial, but temporary pain relief, and the effect was not significantly different from injections of a corticosteroid combined with a local anesthetic. Subjects were selected by a single test block, and the neurolytic procedure was guided by anatomical landmarks and nerve stimulation. A stricter patient selection and an US-guided technique might have improved the results. The authors concluded that these findings question the value of occipital cryoneurolysis for a chronic pain condition like CEH. They stated that occipital cryoneurolysis may be considered when non-invasive treatments appear insufficient, but only for patients who have responded substantially to test blocks. Furthermore, a risk of local scar and neuroma formation by repeated cryoneurolysis, leading to neuropathic pain has been discussed by other researchers.
Cryoneurolysis for the Treatment of Peripheral Neuropathic Pain / Phantom Limb Pain
Moesker and associates (2014) noted that the pathophysiology of phantom limb pain (PLP) is multi-factorial. It probably starts in the periphery and is amplified and modified in the central nervous system (CNS). A small group of patients with PLP were questioned as to the portion of the phantom limb affected by pain (e.g., "great toe," "thumb"). In the stump, the corresponding amputated nerve was located with a nerve stimulator. With correct placement and stimulation, the PLP could then be reproduced or exacerbated. A small dose of local anesthesia was then injected, resulting in the disappearance of the PLP. If a peripheral nerve injection gave temporary relief, the final treatment was cryoanalgesia at this location. Evaluation of 5 patients, followed for at least 2.5 years, yielded the following results: 3 patients had excellent results (100 %, 95 %, and 90 % decrease in complaints, respectively), 1 patient had an acceptable result (40 % decrease), and 1 patient had only a 20 % decrease in pain. The authors concluded that although both central and peripheral components are likely involved in PLP, treatment of a peripheral pain locus with cryoanalgesia should be considered. These researchers proposed the identification of a peripheral etiology may help match patients to an appropriate therapy, and cryoanalgesia may result in long-term relief of PLP.
Yoon and colleagues (2016) examined the safety and efficacy of cryoneurolysis in patients with refractory peripheral neuropathic pain. A total of 22 patients referred for cryoneurolysis of refractory peripheral neuropathy were recruited prospectively from July 2011 to July 2013. The mean patient age was 49.5 years, and 41 % of patients were women; US imaging of the involved nerves was used for guidance. Percutaneous ablations were performed with a PerCryo 17R device. Pain levels were recorded on a VAS (scores 0 to 10) before and at 1, 3, 6, 9, and 12 months after the procedure, and complications were documented. Mean pain levels were 8.3 ± 1.9 before intervention and 2.3 ± 2.5 at 1 month, 3.2 ± 2.5 at 3 months, 4.7 ± 2.7 at 6 months, and 5.1 ± 3.7 at 12 months afterward. A Wilcoxon rank-sum test was performed and showed a statically significant decrease between pre- and post-procedural pain scores. There were no complications from the procedures. The authors concluded that cryoneurolysis caused a significant decrease in self-reported pain scores in patients with chronic refractory neuropathic pain, with moderately long-term relief. Cryoneurolysis is an additional therapy that can alleviate severe chronic neuropathic pain.
Cryoneurolysis for the Treatment of Acute Pain
Ilfeld and Finneran (2020) noted that 2 regional analgesic modalities currently cleared by the Food and Drug Administration (FDA) hold promise to provide post-operative analgesia free of many of the limitations of both opioids and local anesthetic-based techniques. Cryoneurolysis (Iovera) uses exceptionally low temperature to reversibly ablate a peripheral nerve, resulting in temporary analgesia. Where applicable, it offers a unique option given its extended duration of action measured in weeks to months after a single application. Percutaneous peripheral nerve stimulation (PNS) involves inserting an insulated lead via a needle to lie adjacent to a peripheral nerve. Analgesia is produced by introducing electrical current with an external pulse generator. It is a unique regional analgesic in that it does not induce sensory, motor, or proprioception deficits and is cleared for up to 60 days of use. However, both modalities have limited validation when applied to acute pain, and RCTs are needed to define both benefits and risks.
Cryoneurolysis for the Treatment of Chronic Head Pain Secondary to Occipital Neuralgia
Grigsby and colleagues (2021) noted that treatment of chronic pain associated with occipital neuralgia (ON) is complex, and no consensus statement or guidelines have been published for ON management. In a prospective, multi-center, non-randomized, pilot study, these researchers examined the safety and effectiveness of cryoneurolysis for the management of ON-associated chronic pain. They evaluated the degree and duration of clinical effect of cryoneurolysis therapy for reducing pain in patients diagnosed with unilateral or bilateral ON. The primary outcome measure was improvement in pain due to ON from baseline to day 7, measured on an 11-point NRS for pain. Secondary outcome measures included duration of treatment effects and safety events, including anticipated observations and adverse events (AEs). Treatment effect was examined at days 7, 30, and 56 by asking the patient if they were continuing to experience a treatment effect, with potential responses of "effect", "no effect", or "no longer effective". A post-treatment questionnaire examined patient satisfaction. A total of 26 patients (9 men, and 17 women) with a mean age of 49.1 years enrolled and completed the study. A total of 64 % (16/25) of subjects reported a clinically important improvement of greater than or equal to 2 points in NRS pain scores at day 7; similar results persisted to day 30. Treatment effects were reported by 50 % (13/26) of subjects at day 30, with a continued effect reported by 35 % (9/26) of subjects at day 56. Overall, approximately 70 % of subjects were satisfied with treatment at 7, 30, and 56 days. No serious anticipated observations, AEs, or unanticipated adverse device effects were reported. The authors concluded that cryoneurolysis provided significant relief from pain associated with ON of less than or equal to 30 days after treatment and had an acceptable safety profile. Moreover, these researchers stated that the findings of pilot study support further investigation of cryoneurolysis for relief of chronic pain associated with ON.
The authors stated that the main drawback of this study was its uncontrolled, unblinded design, which precluded a comparison of the investigated treatment with other ON treatments. Although this was a prospective study, the lack of a control group likened this pilot study to a case-series study and introduced potential for bias; thus, the effectiveness reported in this report should be interpreted carefully. Furthermore, the small population size included in this study (n = 26) limited the generalizability of these findings. Finally, this study did not include outcome measures to examine the impact of cryoneurolysis on subject’ quality of life (QOL; e.g., PQRST, QISS TAPED). However, these drawbacks did not preclude the use of this preliminary study in informing future, more rigorous, clinical trials. While any conclusions drawn from this pilot study must be limited, the results provide foundational knowledge on the degree and duration of cryoneurolysis effect to support larger, controlled studies of this treatment in patients with ON. Future clinical studies of cryoneurolysis for the treatment of chronic head pain secondary to ON should include a comparator group (e.g., placebo or sham procedure, or active control of another ON treatment); a randomized design; more thorough characterization of the participant population at baseline, including the duration of chronic pain associated with ON; and comparisons of both NRS pain scores and QOL measures (e.g., PQRST, QISS TAPED) between treatment groups.
Pre-Operative Cryoneurolysis for Pain Management Following Total Knee Arthroplasty
In a retrospective, single-center study, Urban et al (2020) examined if cryoneurolysis of superficial genicular nerves combined with standard care (SOC) decreased post-operative opioids and pain after total knee arthroplasty (TKA). Patients who received standardized cryoneurolysis before TKA were compared with a historical control group including patients who underwent TKA without cryoneurolysis. Both groups received a similar peri-operative multi-modal pain management protocol. The primary outcome was opioid intake at various time-points from hospital stay to 6 weeks after discharge. Additional outcomes included pain, hospital LOS, and range of motion (ROM). The analysis included 267 patients (cryoneurolysis group: n = 169; control group: n = 98). During the hospital stay, the cryoneurolysis group had 51 % lower daily morphine milligram equivalents (MMEs) (47 versus 97 MMEs; ratio estimate, 0.49 (95 % CI: 0.43 to 0.56; p < 0.0001) and 22 % lower mean pain score (ratio estimate, 0.78 (95 % CI: 0.70 to 0.88; p < 0.0001) versus the control group. The cryoneurolysis group received significantly fewer cumulative MMEs, including discharge prescriptions, than the control group at week 2 (855 versus 1,312 MMEs; ratio estimate, 0.65 (95 % CI: 0.59 to 0.73; p < 0.0001) and week 6 (894 versus 1,406 MMEs; ratio estimate, 0.64 (95 % CI: 0.57 to 0.71; p < 0.0001). The cryoneurolysis group had significant 44 % reduction in overall hospital LOS (p < 0.0001) and greater flexion degree at discharge (p < 0.0001). The authors concluded the findings of this retrospective study suggested that, when added to a multi-modal TKA pain protocol, pre-operative cryoneurolysis provided superior pain control and allowed patients to take fewer opioids during hospitalization and during the 6-week recovery period than a multi-modal TKA pain protocol alone.
The authors stated that this study had several drawbacks. First, this study was retrospective; thus, patients were not randomized between treatments. These factors precluded the ability to determine causality, given that it was possible that variables other than the addition of cryoneurolysis to a multi-modal pain protocol may have contributed to the observed reductions in pain and opioid consumption. When the practice in this study began to use cryoneurolysis in 2018, there was limited information on its use in TKA, which necessitated ongoing protocol refinement and optimization, including optimization of the US-guided technique for identifying the femoral cutaneous nerves and changes in the type of needle tip used to administer cryoneurolysis. Because of this changing of the cryoneurolysis protocol over time, TKA procedures conducted in 2018 were excluded from the current analysis to enable more reliable comparisons between patients treated with versus without a standardized cryoneurolysis procedure. This approach resulted in a time gap between the cryoneurolysis group (2019 to 2020) and the comparator control group (2017). However, no relevant changes were made to the multi-modal protocol over this time period. Of note, the adjusted mean total opioid prescription at discharge was significantly lower in the more contemporary cryoneurolysis group (2019 to 2020) than that in the control group (2017); as such, changes in opioid-prescribing patterns over time (e.g., greater awareness of risks of opioids, greater understanding that lower doses of opioids could provide effective analgesia) could have impacted the opioid prescription outcomes. However, the authors believed that this was unlikely because the practice did not formally change their opioid-prescribing policy over this time period, and the lower pain scores and opioid consumption observed during the hospital stay in the cryoneurolysis versus the control group were consistent with reduced opioid requirements at discharge in the cryoneurolysis group compared with the control group. Ultimately, even if opioid reductions between the cryoneurolysis and control groups were influenced by greater awareness of the need to reduce opioid prescriptions, the short-term pain outcomes and long-term functional outcomes with cryoneurolysis were optimized, which supported the effectiveness of cryoneurolysis in managing pain and optimizing recovery. Second, it was possible that a trend toward reduced hospital LOS after TKA may partially explain the significant reduction in LOS for the patients who received cryoneurolysis compared with the control group, given that the patients who received cryoneurolysis were treated more than 1 year later. Third, limited pre-operative data were available for the study sample, and pre-operative opioid use, which is a strong predictor of the amount and duration of post-operative opioid use after TKA, may not have been fully captured; this may have affected the ability to reliably examine between-group differences in this potentially confounding variable. Of note, a greater proportion of patients in the cryoneurolysis group in 2019 to 2020 (96 %) had no prior opioid exposure compared with the control group from 2017 (81 %). These researchers believed that this trend could be in part related to a decreased likelihood of primary care providers to prescribe opioids for osteoarthritis (OA) pain control over time because of increased awareness of the opioid epidemic. Because it was not possible to determine if pre-operative exposure may have played a role in the significant difference between groups in opioid prescriptions at the 2-week follow-up, further study is needed to determine the influence of pre-operative opioid exposure on post-operative opioid use in patients receiving cryoneurolysis. Fourth, the use of a single site and surgeon allowed for excellent control over implementation of the multi-modal pain protocol and surgical technique; however, this also limited the generalizability of findings. Fifth, pain data were not available to compare groups after discharge. Nonetheless, given that patients in the cryoneurolysis group showed improved functional outcomes and were prescribed significantly fewer cumulative opioids than patients in the control group, it was reasonable to assume that pain intensity in the cryoneurolysis group was not higher than that in the control group. Sixth, because this was a retrospective study with historical controls, other confounding factors could have influenced study outcomes. However, potentially confounding variables (i.e., BMI, prior opioid exposure, age, and ASA physical status classification) were included in the multi-variable regression model to optimize comparison of the 2 groups. Seventh, cost-effectiveness was not assessed in this study, which would benefit from further assessment in a separate study. Finally, data pertaining to health-care costs were not included in this study. Despite a prior study suggesting that opioid prescriptions were associated with increased health-care costs, further study is needed to determine if cryoneurolysis results in potential cost-savings for patients.
In a single-center study, Mihalko et al (2021) hypothesized that pre-operative cryoneurolysis of the superficial genicular nerves in patients with OA would decrease post-operative opioid use relative to SOC treatment in patients undergoing TKA. Patients received either cryoneurolysis (intent-to-treat [ITT]: n = 62) or SOC (ITT: n = 62). The cryoneurolysis group received cryoneurolysis of the superficial genicular nerves 3 to 7 days before surgery plus a similar pre-operative, intra-operative, and post-operative pain management protocol as the SOC group. The primary endpoint was cumulative opioid consumption in total daily MMEs from discharge to the 6-week study follow-up assessment. Secondary endpoints included changes in pain and functional scores. Primary and secondary endpoints were examined using ITT and per-protocol (PP) analyses. The primary endpoint was not met in the ITT analysis (4.8 [cryoneurolysis] versus 6.1 [SOC] mg; p = 0.0841) but was met in the PP analysis (4.2 versus 5.9 mg; p = 0.0186) after excluding patients with medication deviations or missing follow-up data. Compared with the SOC group, the cryoneurolysis group had improved functional scores and numerical improvements in pain scores across all follow-up assessments, with significant improvements observed in current pain from baseline to the 72-hour and 2-week follow-up assessments and pain in the past week from baseline to the 12-week follow-up assessment. The authors concluded that findings from the PP analysis suggested that pre-operative cryoneurolysis may be considered as a part of multi-modal pain management to minimize opioid use while reducing pain and improving knee function after surgery. Moreover, these researchers stated that future studies should examine the safety, effectiveness, and opioid-sparing benefits of cryoneurolysis in patients with prior long-term opioid use undergoing TKA.
The authors stated that a drawback of this study was the lack of a sham control group. Although these investigators could not discount the possibility that the improved outcomes in the cryoneurolysis group were partially attributable to a placebo effect, they noted that results from a sham-controlled study of cryoneurolysis for the treatment of knee OA pain demonstrated a statistically significant reduction in pain in patients who received cryoneurolysis. Furthermore, for the Knee Injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS JR) scores, the highest (worst) score was imputed for questions that patients did not answer; regardless of this imputation that would bias against the study intervention, cryoneurolysis improved knee function outcome scores across multiple time-points. The use of a single site allowed for greater control over pain management and physical therapy protocols. Because this study was conducted at a single clinical site, the findings may not be generalizable to larger, more diverse populations, especially given that there appeared to be wide variation in post-operative opioid prescribing habits even within a single healthcare system, necessitating system-wide quality improvement programs. Some patients in the present study did not receive spinal anesthesia and instead received general anesthesia. General anesthesia is associated with a higher rate of infection and a longer hospital LOS compared with spinal anesthesia. Given these data, it may be expected that the use of general anesthesia could bias against the outcomes assessed in this study. However, despite the numerically larger number of patients in the cryoneurolysis group who received general anesthesia compared with the SOC group, improved pain management and function were observed with this intervention. Furthermore, while patients who were not prescribed tramadol were excluded from the PP analysis, tramadol use was not directly measured; as such, it is not possible to evaluate how patient non-adherence could have affected observed outcomes. Also, patient satisfaction measures and cost effectiveness were not analyzed, and future studies incorporating these analyses may help provide a comprehensive understanding of treatment effects beyond clinical outcomes. Finally, given the number of medical deviations that could have confounded patient outcomes, results from the PP analysis were likely more meaningful than the ITT analysis; however, the PP analysis should be interpreted with caution because of the small sample size and because it was more likely to be biased toward the null hypothesis than the ITT analysis.
Appendix
Selection Criteria of Cryoanalgesia for Trigeminal Neuralgia
- Members have experienced pain for at least 6 months, and
- Members have tried and failed pharmacotherapies (e.g., baclofen, carbamazepine, phenytoin), or are unable to tolerate the side effects of the medication.
Repeat cryoanalgesia may be medically necessary every 6 months.
References
The above policy is based on the following references:
Cryoanalgesia for Trigeminal Neuralgia
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Intra-Operative and Post-Operative Cryoanalgesia for the Management of Post-Thoracotomy Pain
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Cold Therapy Units and Hot/Ice Machine
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Therapeutic Induction of Intra-Brain Hypothermia for Concussion Management
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Miscellaneous
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